Optimized network inference for immune diseased single cells.

Introduction: Mathematical models are powerful tools that can be used to advance our understanding of complex diseases. Autoimmune disorders such as systemic lupus erythematosus (SLE) are highly heterogeneous and require high-resolution mechanistic approaches. In this work, we present ONIDsc, a single-cell regulatory network inference model designed to elucidate immune-related disease mechanisms in SLE.

Overview of Molecular Diagnostics in Irish Clinical Oncology.

Background: Molecular diagnostics are critical for informing cancer patient care. In Ireland, the National Cancer Control Programme (NCCP) develops cancer therapy regimens, which include relevant information on molecular indications. Here, we present a collated overview of the current molecular indications of all NCCP systemic anti-cancer therapy regimens and the funding statuses of their associated drugs.

The fibrin-derived peptide FX06 protects human pulmonary endothelial cells against the COVID-19-triggered cytokine storm.

Introduction: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major health emergency since its emergence in late 2019. Endothelial dysfunction is a hallmark of COVID-19, leading to severe illness, i.e.

A temporal model of tumor-immune dynamics during the metastatic progression of high-grade serous ovarian cancer.

Patients with high-grade serous ovarian cancer (HGSOC) typically present with widespread metastasis, obscuring a temporal understanding of tumor-immune dynamics. To address this, we perform multi-site global proteomics alongside matched immunohistochemistry (IHC) for CD4⁺ and CD8⁺ tumor-infiltrating lymphocytes (TILs) in patient samples. We order the protein expression profiles using an unbiased pseudotime analysis, recapitulating clinical observations of metastatic progression, and providing a framework to explore tumor-immune dynamics from localized to metastatic disease.

Invisible spectrum: a model for minority community public engagement in cancer research.

Background: Ethnic minority communities are often recognised as experiencing decreased accessibility to vital medical services as well as increased barriers to participation in research studies. These issues stem from a variety of social, cultural and economic factors, all of which must be taken into consideration when designing engagement initiatives for a particular community. Invisible Spectrum is an annual engagement initiative which seeks to promote effective communication and outreach to often-overlooked ethnic minority communities within Ireland, primarily those of Bangladeshi origin.

Direct cell interactions potentially regulate transcriptional programmes that control the responses of high grade serous ovarian cancer patients to therapy.

The tumour microenvironment is composed of a complex cellular network involving cancer, stromal and immune cells in dynamic interactions. A large proportion of this network relies on direct physical interactions between cells, which may impact patient responses to clinical therapy. Doublets in scRNA-seq are usually excluded from analysis.

Erratum: BTLA and PD-1 signals attenuate TCR-mediated transcriptomic changes.

[This corrects the article DOI: 10.1016/j.isci.

eIF4F controls ERK MAPK signaling in melanomas with and mutations.

The eIF4F translation initiation complex plays a critical role in melanoma resistance to clinical BRAF and MEK inhibitors. In this study, we uncover a function of eIF4F in the negative regulation of the rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling pathway. We demonstrate that eIF4F is essential for controlling ERK signaling intensity in treatment-naïve melanoma cells harboring or mutations.

Spatial proteomics and transcriptomics of the maternal-fetal interface in placenta accreta spectrum.

In severe Placenta Accreta Spectrum (PAS), trophoblasts gain deep access in the myometrium (placenta increta). This study investigated alterations at the fetal-maternal interface in PAS cases using a systems biology approach consisting of immunohistochemistry, spatial transcriptomics and proteomics. We identified spatial variation in the distribution of CD4, CD3 and CD8 T-cells at the maternal-interface in placenta increta cases.

Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges for targeted clinical interventions due to prevalent KRAS mutations, rendering PDAC resistant to RAF and MEK inhibitors (RAFi and MEKi). In addition, responses to targeted therapies vary between patients. Here, we explored the differential sensitivities of PDAC cell lines to RAFi and MEKi and developed an isogenic pair comprising the most sensitive and resistant PDAC cells.

BTLA and PD-1 signals attenuate TCR-mediated transcriptomic changes.

T cell co-inhibitory immune checkpoints, such as PD-1 or BTLA, are bona fide targets in cancer therapy. We used a human T cell reporter line to measure transcriptomic changes mediated by PD-1- and BTLA-induced signaling. T cell receptor (TCR)-complex stimulation resulted in the upregulation of a large number of genes but also in repression of a similar number of genes.

Genomic and Transcriptomic Analysis of a Patient with Early-Onset Colorectal Cancer and Therapy-Induced Focal Nodular Hyperplasia: A Case Report.

Early-onset colorectal cancer (EOCRC), defined as colorectal cancer in individuals under 50 years of age, has shown an alarming increase in incidence worldwide. We report a case of a twenty-four-year-old female with a strong family history of colorectal cancer (CRC) but without an identified underlying genetic predisposition syndrome. Two years after primary surgery and adjuvant chemotherapy, the patient developed new liver lesions.

A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer.

Unlabelled: Racial disparities between Black/African Americans (AA) and White patients in colorectal cancer are an ever-growing area of concern. Black/AA show the highest incidence and have the highest mortality among major U.S.

Memory of stochastic single-cell apoptotic signaling promotes chemoresistance in neuroblastoma.

Gene expression noise is known to promote stochastic drug resistance through the elevated expression of individual genes in rare cancer cells. However, we now demonstrate that chemoresistant neuroblastoma cells emerge at a much higher frequency when the influence of noise is integrated across multiple components of an apoptotic signaling network. Using a JNK activity biosensor with longitudinal high-content and in vivo intravital imaging, we identify a population of stochastic, JNK-impaired, chemoresistant cells that exist because of noise within this signaling network.

Oncotherapeutic Strategies in Early Onset Colorectal Cancer.

Early onset colorectal cancer (EOCRC), defined as colorectal cancers in patients aged less than 50 years, is becoming an increasingly common issue, globally. Since 1994, the incidence of this condition has been rising by 2% annually. Approximately one in five patients under 50 years of age diagnosed with colorectal cancer have an underlying genetic predisposition syndrome.